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Eur J Cancer. 2016 Feb;54:139-148. doi: 10.1016/j.ejca.2015.11.016. Epub 2016 Jan 5.

Immune-related adverse events with immune checkpoint blockade: a comprehensive review.

Author information

1
Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Internal Medicine and Clinical Immunology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Bicêtre, F-94275 Le Kremlin Bicêtre, France. Electronic address: jean-marie.michot@gustaveroussy.fr.
2
Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
3
Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
4
Gastroenterology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Bicêtre, F-94275 Le Kremlin Bicêtre, France; Université Paris Sud 11, F-94275 Le Kremlin-Bicêtre, France.
5
Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
6
Internal Medicine and Clinical Immunology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Bicêtre, F-94275 Le Kremlin Bicêtre, France; Université Paris Sud 11, F-94275 Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, Division of Immunovirology, IDMIT, F-92265 Fontenay-aux-Roses, France; INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, F-94276 Le Kremlin-Bicêtre, France.
7
Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Internal Medicine and Clinical Immunology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Bicêtre, F-94275 Le Kremlin Bicêtre, France.

Abstract

Cancer immunotherapy is coming of age; it has prompted a paradigm shift in oncology, in which therapeutic agents are used to target immune cells rather than cancer cells. The first generation of new immunotherapies corresponds to antagonistic antibodies that block specific immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. Targeting these checkpoints in patients living with cancer had led to long-lasting tumour responses. By unbalancing the immune system, these new immunotherapies also generate dysimmune toxicities, called immune-related adverse events (IRAEs) that mainly involve the gut, skin, endocrine glands, liver, and lung but can potentially affect any tissue. In view of their undisputed clinical efficacy, anti-CTLA-4 and anti-PD-1 antibodies are entering in the routine oncological practice, and the number of patients exposed to these drugs will increase dramatically in the near future. Although steroids can be used to treat these IRAEs, the associated immunosuppression may compromise the antitumour response. Oncologists must be ready to detect and manage these new types of adverse events. This review focuses on the mechanisms of IRAE generation, putative relationship between dysimmune toxicity and antitumour efficacy, as a basis for management guidelines.

KEYWORDS:

Anti-PD-1 antibody; Cytotoxic T-lymphocyte-associated antigen 4; Immune checkpoint blockade; Immune-related adverse events; Tumour neoantigen

PMID:
26765102
DOI:
10.1016/j.ejca.2015.11.016
[Indexed for MEDLINE]

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